PROJECT SUMMARY Recent national data indicate a higher prevalence of osteoporosis (OP) among Hispanics, compared with non- Hispanic whites or blacks. As one of the fastest growing segments of the U.S. population, this group is projected to have the largest increase in OP-related fracture from 2005 to 2025. Hispanic adults of Caribbean origin have been shown to have poorer bone quality than non-Hispanic whites. Puerto Ricans, in particular, have higher prevalence of OP than previously appreciated. Although higher bone mineral density (BMD) has been noted in those with type 2 diabetes (T2D), T2D contributes to compromised bone strength, cortical defects and increased cortical porosity increasing risk of fracture. This is of particular concern for Puerto Ricans who have a high prevalence of T2D. One mechanism for poor bone quality among those with T2D is the accumulation of advanced glycation end-products (AGE), which affect bone mechanical properties. Animal studies suggest that antioxidant activity from vitamin B6 may inhibit AGE formation. Greater plasma pyridoxyl- 5'-phosphate (PLP, vitamin B6) concentration and intake of vitamin B6 has been associated with less bone loss over time and reduced risk of fracture; but mechanisms are unclear. Trabecular bone score (TBS), a novel measure of trabecular microarchitecture of the lumbar spine, is indicative of fragility fracture risk, even among those with normal BMD; however, research on TBS for assessing bone quality is limited and urgently needed. Further, assessment of bone strength by novel micro-indentation may elucidate differences in bone quality among T2D at risk for OP. Therefore, our central hypothesis is that Puerto Rican adults with T2D will have poor bone strength (micro-indentation), and greater loss of TBS at the spine and of BMD at the spine and hip compared to individuals without T2D; and that this will be moderated by high plasma AGE concentration. Our secondary hypothesis is that greater plasma PLP will be associated with lower plasma AGE and therefore higher bone strength (micro-indentation), and less loss of TBS and BMD over time. All available 860 Puerto Rican adults who participated in the Boston Puerto Rican Osteoporosis Study with valid BMD data will be invited to participate in the proposed study. Participants will complete a questionnaire, a repeat DXA scan, undergo bone micro-indentation, skin autofluorescence measurement of AGES and provide a fasting blood sample. The proposed research is innovative in the inclusion of TBS as a measure of bone quality, micro- indentation to evaluate bone strength, the examination of AGE as an effect modifier linking diabetes and bone health, and the consideration of PLP as a factor in AGE in a longitudinal study. This work is urgently needed to improve our understanding of complex risk factors for bone health, and to provide important information for the development of future interventions to prevent bone loss and fracture risk, particularly in high-risk populations with health disparities.